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Journal of Complementary and Integrative Medicine

Editor-in-Chief: Lui, Edmund

Ed. by Ko, Robert / Leung, Kelvin Sze-Yin / Saunders, Paul / Suntres, PH. D., Zacharias

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Comparison of anticancer effect of Pleurotus ostreatus extract with doxorubicin hydrochloride alone and plus thermotherapy on erythroleukemia cell line

Alireza Ebrahimi
  • Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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/ Amir Atashi
  • Corresponding author
  • Stem Cells and Tissue Engineering Research Center, Shahroud University of Medical Sciences, Shahroud 3614773955, Iran
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/ Masoud Soleimani
  • Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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/ Maedeh Mashhadikhan
  • Department of Biology, Faculty of Sciences, Tehran Sciences and Research Branch, Islamic Azad University, Tehran, Iran
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/ Ahmadreza barahimi
  • Department of Medical Mycology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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/ Saeid Kaviani
  • Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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Published Online: 2017-12-19 | DOI: https://doi.org/10.1515/jcim-2016-0136



Recent studies have introduced Pleurotus ostreatus (Pleurotaceae) as a herbal medicine for treating different types of cancer. This survey utilizes P. ostreatus and doxorubicin hydrochloride (DOX) alone and then with hyperthermia to investigate the erythroleukemia cell line. This study evaluates and compares the apoptotic and necrotic effects of various treatments on the KG-1 cell line.


The proliferation of KG-1 cells was measured by using a tetrazolium salt (MTT)-based colorimetric assay during 96 h after treatment by gradient dilutions of 100 ng/mL to 100 mg/mL of P. ostreatus methanol extract and then the minimum inhibitory concentration (MIC) was determined and was applied in additional experiments. Afterward, the cells were treated using P. ostreatus extract, DOX (6.95 mg/L), and hyperthermia (42 and 44 °C), separately and then applying hyperthermia. Finally, the ratios of apoptosis and necrosis after 24 h incubation were evaluated by using flow cytometry.


The MIC of the extract was determined (1 mg/mL), which significantly increased the ratio of apoptosis rather than necrosis, whereas the DOX treatment primarily induced necrosis on the KG-1 cells. The anticancer effects of the mushroom extract were significantly increased when it was combined with thermotherapy, which exhibited apoptotic effects at 42 °C but induced necrosis at 44 °C.


The results suggest that P. ostreatus extract induces apoptosis on KG-1 cells and its anticancer effects are significantly increased in combination with thermotherapy. Therefore, P. ostreatus could be considered as an alternative with anticancer effect for further studies in erythroleukemia patients.

Keywords: apoptosis; chemotherapy; herbal medicine; KG-1 cells; physical medicine


  • [1]

    Bettaieb A, Wrzal PK, Averill-Bates DA. Hyperthermia: cancer treatment and beyond. In: Rangel L, editors. Cancer treatment-conventional and innovative approaches. California, USA: InTech; 2013. p. 257–83.Google Scholar

  • [2]

    Rybiński M, Szymańska Z, Lasota S, Gambin A. Modelling the efficacy of hyperthermia treatment. J R Soc Interface. 2013;10:20130527.Web of ScienceCrossrefPubMedGoogle Scholar

  • [3]

    Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, et al. Hyperthermia in combined treatment of cancer. Lancet Oncol. 2002;3:487–97.CrossrefPubMedGoogle Scholar

  • [4]

    Kampinga HH. Thermotolerance in mammalian cells. Protein denaturation and aggregation, and stress proteins. J Cell Sci. 1993;104:11–17.PubMedGoogle Scholar

  • [5]

    Beere HM. Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways. J Clin Invest. 2005;115:2633–39.CrossrefPubMedGoogle Scholar

  • [6]

    Calderon-Montano JM, Burgos-Moron E, Perez-Guerrero C, Salvador J, Robles A, Lopez-Lazaro M. Role of the intracellular pH in the metabolic switch between oxidative phosphorylation and aerobic glycolysis-relevance to cancer. Web Med Cent Cancer. 2011;2:WMC001716.Google Scholar

  • [7]

    McCarty MF, Whitaker J. Manipulating tumor acidification as a cancer treatment strategy. Altern Med Rev. 2010;15:264–72.PubMedGoogle Scholar

  • [8]

    Kong G, Anyarambhatla G, Petros WP, Braun RD, Colvin OM, Needham D, et al. Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res. 2000;60:6950–57.Google Scholar

  • [9]

    Pawlik A, Nowak JM, Grzanka D, Gackowska L, Michalkiewicz J, Grzanka A. Hyperthermia induces cytoskeletal alterations and mitotic catastrophe in p53-deficient H1299 lung cancer cells. Acta Histochem. 2013;115:8–15.CrossrefWeb of SciencePubMedGoogle Scholar

  • [10]

    Raghunand N, He X, Van Sluis R, Mahoney B, Baggett B, Taylor C, et al. Enhancement of chemotherapy by manipulation of tumour pH. Br J Cancer. 1999;80:1005–11.CrossrefPubMedGoogle Scholar

  • [11]

    Ahmed K, Zaidi SF. Treating cancer with heat: hyperthermia as promising strategy to enhance apoptosis. J Pak Med Assoc. 2013;63:504–08.PubMedGoogle Scholar

  • [12]

    Arai Y, Kondo T, Tanabe K, Zhao Q-L, Li F-J, Ogawa R, et al. Enhancement of hyperthermia-induced apoptosis by local anesthetics on human histiocytic lymphoma U937 cells. J Biol Chem. 2002;277:18986–93.PubMedCrossrefGoogle Scholar

  • [13]

    Bassil NM, Abdel-Massih R, El-Chami N, Smith CA, Baydoun E. Pleurotus ostreatus and Ruscus aculeatus extracts cause non-apoptotic jurkat cell death. J Plant Stud. 2012;1:14–24.Google Scholar

  • [14]

    Bobek P, Ozdin L. The mushroom Pleurotus ostreatus accelerates plasma very-low-density lipoprotein clearance in hypercholesterolemic rat. Physiol Res. 1993;43:205–06.Google Scholar

  • [15]

    Dos Santos LF, Zanatta AL, Soccol VT, Torres MF, Bonatto SJR, Rubel R, et al. Hypolipidemic and antiatherosclerotic potential of Pleurotus ostreatus, cultivated by submerged fermentation in the high-fat diet fed rats. Biotechnol Bioproc Eng. 2013;18:201–08.CrossrefGoogle Scholar

  • [16]

    Morris H, Marcos J, Llauradó G, Fontaine R, Tamayo V, García N, et al. Immunomodulating effects of hot-water extract from Pleurotus ostreatus mycelium on cyclophosphamide treated mice. Micol Apl Int. 2003;15:7–13.Google Scholar

  • [17]

    Jedinak A, Sliva D. Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway. Int J Oncol. 2008;33:1307–13.Web of SciencePubMedGoogle Scholar

  • [18]

    Wu J-Y, Chen C-H, Chang W-H, Chung K-T, Liu Y-W, Lu F-J, et al. Anti-cancer effects of protein extracts from Calvatia lilacina, Pleurotus ostreatus and Volvariella volvacea. Evid Based Complement Alternat Med. 2011;2011:982368.PubMedGoogle Scholar

  • [19]

    Olufemi AE, Terry AO, Kola OJ. Anti-leukemic and immunomodulatory effects of fungal metabolites of Pleurotus pulmonarius and Pleurotus ostreatus on benzene-induced leukemia in Wister rats. Korean J Hematol. 2012;47:67–73.CrossrefPubMedGoogle Scholar

  • [20]

    Park S, Picard F, Dreyfus F. Erythroleukemia: a need for a new definition. Leukemia. 2002;16:1399–401.CrossrefPubMedGoogle Scholar

  • [21]

    Kowal‐Vern A, Mazzella FM, Cotelingam JD, Shrit MA, Rector JT, Schumacher HR. Diagnosis and characterization of acute erythroleukemia subsets by determining the percentages of myeloblasts and proerythroblasts in 69 cases. Am J Hematol. 2000;65:5–13.CrossrefPubMedGoogle Scholar

  • [22]

    Mitra S, Gaur U, Ghosh P, Maitra A. Tumour targeted delivery of encapsulated dextran–doxorubicin conjugate using chitosan nanoparticles as carrier. J Control Release. 2001;74:317–23.PubMedCrossrefGoogle Scholar

  • [23]

    Firestone RA. Anti-cancer effects of novel doxorubicin prodrug PDOX in MCF-7 breast cancer cells. J Huazhong Univ Sci Technol. 2014;34:521–28.CrossrefGoogle Scholar

  • [24]

    Mackey MA, Anolik SL, Roti JLR. Cellular mechanisms associated with the lack of chronic thermotolerance expression in HeLa S3 cells. Cancer Res. 1992;52:1101–06.PubMedGoogle Scholar

  • [25]

    Huang C, Li Y, Cao P, Xie Z, Qin Z. Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells. J Huazhong Univ Sci Technol. 2011;31:488–96.CrossrefGoogle Scholar

  • [26]

    Lin S, Ching LT, Lam K, Cheung PC. Anti-angiogenic effect of water extract from the fruiting body of Agrocybe aegerita. LWT-Food Sci Tech. 2017;75:155–63.CrossrefGoogle Scholar

  • [27]

    Eynali S, Khoei S, Khoee S, Esmaelbeygi E. Evaluation of the cytotoxic effects of hyperthermia and 5-fluorouracil-loaded magnetic nanoparticles on human colon cancer cell line HT-29. Int J Hyperthermia. 2016;1:1–9.Web of ScienceGoogle Scholar

  • [28]

    Van Der Zee J, González D, Van Rhoon GC, Van Dijk JD, Van Putten WL, Hart AA. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Lancet. 2000;355:1119–25.PubMedCrossrefGoogle Scholar

  • [29]

    Lavi I, Friesem D, Geresh S, Hadar Y, Schwartz B. An aqueous polysaccharide extract from the edible mushroom Pleurotus ostreatus induces anti-proliferative and pro-apoptotic effects on HT-29 colon cancer cells. Cancer Lett. 2006;244:61–70.CrossrefPubMedGoogle Scholar

About the article

Received: 2017-02-28

Accepted: 2017-10-16

Published Online: 2017-12-19

Author contributions: A. Ebrahimi, A. Barahimi and A. Atashi conceived and designed the experiments; A. Ebrahimi, A. Atashi performed the experiments; A. Ebrahimi and M. Mashhadikhan analyzed the data; M.soleimani, S. Kaviani contributed reagents/materials/analysis tools; A. Ebrahimi and M. Mashhadikhan wrote the paper.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Human and Animal Rights: This article does not contain any studies with human or animal subjects performed by any of the authors.

Citation Information: Journal of Complementary and Integrative Medicine, Volume 15, Issue 2, 20160136, ISSN (Online) 1553-3840, DOI: https://doi.org/10.1515/jcim-2016-0136.

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